Sebastiano Buti1, Melissa Bersanelli2, Fabiana Perrone1, Marcello Tiseo3, Marco Tucci4, Vincenzo Adamo5, Luigia S Stucci6, Alessandro Russo5, Enrica T Tanda7, Francesco Spagnolo7, Francesca Rastelli8, Federica Pergolesi8, Daniele Santini9, Marco Russano9, Cecilia Anesi9, Raffaele Giusti10, Marco Filetti10, Paolo Marchetti11, Andrea Botticelli12, Alain Gelibter13, Mario Alberto Occhipinti13, Marco Ferrari14, Maria Giuseppa Vitale15, Linda Nicolardi16, Rita Chiari16, Erika Rijavec17, Olga Nigro18, Alessandro Tuzi18, Michele De Tursi19, Pietro Di Marino20, Fabio Conforti21, Paola Queirolo21, Sergio Bracarda22, Serena Macrini22, Stefania Gori23, Federica Zoratto24, Enzo Veltri24, Barbara Di Cocco24, Domenico Mallardo25, Maria Grazia Vitale25, Matteo Santoni26, Leonardo Patruno27, Giampiero Porzio28, Corrado Ficorella27, David J Pinato29, Paolo A Ascierto25, Alessio Cortellini27. 1. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 2. Medical Oncology Unit, University Hospital of Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy. Electronic address: bersamel@libero.it. 3. Medical Oncology Unit, University Hospital of Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy. 4. Medical Oncology Unit, University of Bari, Department of Biomedical Sciences and Human Oncology, Bari, Italy; National Cancer Research Center, Tumori Institute IRCCS Giovanni Paolo II, Bari, Italy. 5. Medical Oncology, A.O. Papardo & Department of Human Pathology, University of Messina, Italy. 6. Medical Oncology Unit, University of Bari, Department of Biomedical Sciences and Human Oncology, Bari, Italy. 7. IRCCS Ospedale Policlinico San Martino, Genova, Italy. 8. Medical Oncology, Fermo Area Vasta 4, Fermo, Italy. 9. Medical Oncology, Campus Bio-Medico University, Rome, Italy. 10. Medical Oncology Unit, Sant' Andrea Hospital of Rome, Rome, Italy. 11. Medical Oncology Unit, Sant' Andrea Hospital of Rome, Rome, Italy; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy; Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 12. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy; Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 13. Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 14. Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 15. Medical Oncology, University Hospital of Modena, Modena, Italy. 16. UOC Oncologia Padova Sud AULSS6 Euganea, Padova, Italy. 17. Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 18. Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy. 19. Department of Medical, Oral & Biotechnological Sciences, University G. D'Annunzio, Chieti-Pescara, Italy. 20. Clinical Oncology Unit, S.S. Annunziata Hospital, Chieti, Italy. 21. Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy. 22. S.C. Medical Oncology, Azienda Ospedaliera S. Maria, Terni, Italy. 23. Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, VR, Italy. 24. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy. 25. Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS Fondazione "G. Pascale", Naples, Italy. 26. Department of Oncology, Macerata Hospital, Macerata, Italy. 27. Medical Oncology Unit, St. Salvatore Hospital, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. 28. Medical Oncology Unit, St. Salvatore Hospital, L'Aquila, Italy. 29. Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Abstract
BACKGROUND: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score. METHODS: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). RESULTS: In the training cohort (n = 217), the median age was 69 years (range: 32-89), and the primary tumours were non-small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60-3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31-3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13-2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort. CONCLUSION: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs.
BACKGROUND: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score. METHODS: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). RESULTS: In the training cohort (n = 217), the median age was 69 years (range: 32-89), and the primary tumours were non-small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60-3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31-3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13-2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort. CONCLUSION: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs.
Authors: F Nelli; A Virtuoso; J R Giron Berrios; D Giannarelli; A Fabbri; E Marrucci; E M Ruggeri Journal: Cancer Chemother Pharmacol Date: 2022-03-18 Impact factor: 3.333
Authors: Marco Russano; Alessio Cortellini; Raffaele Giusti; Alessandro Russo; Federica Zoratto; Francesca Rastelli; Alain Gelibter; Rita Chiari; Olga Nigro; Michele De Tursi; Sergio Bracarda; Stefania Gori; Francesco Grossi; Melissa Bersanelli; Lorenzo Calvetti; Vincenzo Di Noia; Mario Scartozzi; Massimo Di Maio; Paolo Bossi; Alfredo Falcone; Fabrizio Citarella; Francesco Pantano; Corrado Ficorella; Marco Filetti; Vincenzo Adamo; Enzo Veltri; Federica Pergolesi; Mario Alberto Occhipinti; Linda Nicolardi; Alessandro Tuzi; Pietro Di Marino; Serena Macrini; Alessandro Inno; Michele Ghidini; Sebastiano Buti; Giuseppe Aprile; Eleonora Lai; Marco Audisio; Salvatore Intagliata; Riccardo Marconcini; Davide Brocco; Giampiero Porzio; Marta Piras; Erika Rijavec; Francesca Simionato; Clara Natoli; Marcello Tiseo; Bruno Vincenzi; Giuseppe Tonini; Daniele Santini Journal: Cancer Immunol Immunother Date: 2021-08-31 Impact factor: 6.968
Authors: Daniele Santini; Tea Zeppola; Marco Russano; Fabrizio Citarella; Cecilia Anesi; Sebastiano Buti; Marco Tucci; Alessandro Russo; Maria Chiara Sergi; Vincenzo Adamo; Luigia S Stucci; Melissa Bersanelli; Giulia Mazzaschi; Francesco Spagnolo; Francesca Rastelli; Francesca Chiara Giorgi; Raffaele Giusti; Marco Filetti; Paolo Marchetti; Andrea Botticelli; Alain Gelibter; Marco Siringo; Marco Ferrari; Riccardo Marconcini; Maria Giuseppa Vitale; Linda Nicolardi; Rita Chiari; Michele Ghidini; Olga Nigro; Francesco Grossi; Michele De Tursi; Pietro Di Marino; Laura Pala; Paola Queirolo; Sergio Bracarda; Serena Macrini; Stefania Gori; Alessandro Inno; Federica Zoratto; Enrica T Tanda; Domenico Mallardo; Maria Grazia Vitale; Thomas Talbot; Paolo A Ascierto; David J Pinato; Corrado Ficorella; Giampiero Porzio; Alessio Cortellini Journal: J Transl Med Date: 2021-06-24 Impact factor: 5.531